2026-04-27T20:01:50Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/638702025-01-13T07:38:39Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

León, Josefa Escames, Germaine Rodríguez, María I. López, Luis C. Tapias Molina, Victor Entrena, Antonio Camacho, Encarnación Carrión, María D. Gallo, Miguel A. Espinosa, Antonio Tan, Dun‐Xian Reiter, Russel J. Acuña Castroviejo, Darío 2024-01-01T20:50:50Z 2024-01-01T20:50:50Z 2006 Journal of Neurochemistry, Septiembre 2006, vol. 98, n. 6, p. 2023-2033 0022-3042 https://uvadoc.uva.es/handle/10324/63870 10.1111/j.1471-4159.2006.04029.x 2023 6 2033 Journal of Neurochemistry 98 1471-4159 We assessed the effects of melatonin, N(1)-acetyl-N (2)-formyl-5-methoxykynuramine (AFMK) and N(1)-acetyl-5-methoxykynuramine (AMK) on neuronal nitric oxide synthase (nNOS) activity in vitro and in rat striatum in vivo. Melatonin and AMK (10(-11)-10(-3) m), but not AFMK, inhibited nNOS activity in vitro in a dose-response manner. The IC(50) value for AMK (70 microm) was significantly lower than for melatonin (>1 mm). A 20% nNOS inhibition was reached with either 10(-9) m melatonin or 10(-11) m AMK. AMK inhibits nNOS by a non-competitive mechanism through its binding to Ca(2+)-calmodulin (CaCaM). The inhibition of nNOS elicited by melatonin, but not by AMK, was blocked with 0.05 mm norharmane, an indoleamine-2,3-dioxygenase inhibitor. In vivo, the potency of AMK to inhibit nNOS activity was higher than that of melatonin, as a 25% reduction in rat striatal nNOS activity was found after the administration of either 10 mg/kg of AMK or 20 mg/kg of melatonin. Also, in vivo, the administration of norharmane blocked the inhibition of nNOS produced by melatonin administration, but not the inhibition produced by AMK. These data reveal that AMK rather than melatonin is the active metabolite against nNOS, which may be inhibited by physiological levels of AMK in the rat striatum. eng info:eu-repo/semantics/embargoedAccess Inhibition of neuronal nitric oxide synthase activity by N1‐acetyl‐5‐methoxykynuramine, a brain metabolite of melatonin info:eu-repo/semantics/article